Risk factors of cognitive impairment in pediatric epilepsy patients with focal cortical dysplasia

Objective

The purpose of this study was to identify the risk factors of cognitive impairment in pediatric epilepsy patients with focal cortical dysplasia (FCD).

Surgical outcome and predictive factors in adult patients with intractable epilepsy and focal cortical dysplasia

OBJECTIVES: To determine the surgical outcome and prognostic factors in adult patients with intractable epilepsy and focal cortical dysplasia (FCD). MATERIALS AND METHODS: We retrospectively studied the operative outcome in 21 consecutive adult patients with FCD who underwent surgical treatment for intractable partial epilepsy. RESULTS: The mean age at surgery was 32.7 years (range, 18-58 years). The median post-operative follow-up was 2.5 years. The FCD was extratemporal in 11 patients, involved the temporal lobe in 10 patients, and was multilobar in eight patients. Eleven patients (52%) were rendered seizure-free, four patients (19%) had >95% reduction in seizures, and two patients (10%) had an 80-94% reduction in seizures. A seizure-free outcome was associated with shorter duration of epilepsy (P = 0.02). CONCLUSION: Adult patients with FCD may be candidates for surgical treatment of intractable partial epilepsy. Most individuals have neocortical, extrahippocampal seizures and approximately 50% of patients are rendered seizure-free.     

Clinical characteristics and post-surgical outcomes of focal cortical dysplasia subtypes

We retrospectively studied 105 patients with a focal cortical dysplasia (FCD) diagnosed on pathological examination, and investigated the long term postoperative seizure outcomes, different clinical characteristics of the three FCD subtypes, particularly type I and II, and surgical outcomes for each group. FCD is a common cause of drug-resistant epilepsy, which is divided into three different subtypes according to its involvement at different stages of brain development. Each of these groups may have different characteristics and may even have different surgical outcomes. After treatment, 55% of patients were completely seizure-free, with two significant predictive variables for poorer outcomes: focal MRI findings and electrode implantation. FCD type I had relatively poor surgical outcomes compared to FCD type II and type IIIa. Compared with FCD type I, type II, particularly IIb, had a higher frequency of seizure attacks, predominantly located in the extratemporal lobes, and was more readily detected and diagnosed via focal lesions on MRI and localized electroencephalogram abnormalities. FCD type II patients seem to show better surgical outcomes than FCD type I, but the difference was not significant. Larger cohort studies are needed for further evaluation of the seizure outcomes of different FCD subtypes.     

脑发育异常性癫痫脑组织的MDR-1、MRP和GFAP表达一例并文献复习

目的：观察灰质异位性难治性癫痫中多药耐药基因蛋白（MDR-1）、耐药基因相关蛋白（MRP）及胶质纤维酸性蛋白（GFAP）在发育异常性脑组织中的表达情况。方法：对确诊为脑灰质异位性症状性癫痫患者手术切除下病灶组织行免疫组化染色，观察脑组织中MDR-1、MRP及GFAP的表达情况。结果：在手术切除的病灶组织中，除一些增生性的星形胶质细胞同时具上述三种蛋白的阳性标记外，在一些异形的神经元内同时还存在有MDR-1和MRP的阳性表达。结论：灰质异位性难治性癫痫中MDR-1、MRP及GFAP不仅可在一些反应性的星形胶质细胞中表达，而且还可在一些发育异常的异形神经元中表达。     

Developmental origins of cortical hyperexcitability in Huntington's disease: Review and new observations

Huntington's disease (HD), an inherited neurodegenerative disorder that principally affects striatum and cerebral cortex, is generally thought to have an adult onset. However, a small percentage of cases develop symptoms before 20 years of age. This juvenile variant suggests that brain development may be altered in HD. Indeed, recent evidence supports an important role of normal huntingtin during embryonic brain development and mutations in this protein cause cortical abnormalities. Functional studies also demonstrated that the cerebral cortex becomes hyperexcitable with disease progression. In this review, we examine clinical and experimental evidence that cortical development is altered in HD. We also provide preliminary evidence that cortical pyramidal neurons from R6/2 mice, a model of juvenile HD, are hyperexcitable and display dysmorphic processes as early as postnatal day 7. Further, some symptomatic mice present with anatomical abnormalities reminiscent of human focal cortical dysplasia, which could explain the occurrence of epileptic seizures in this genetic mouse model and in children with juvenile HD. Finally, we discuss recent treatments aimed at correcting abnormal brain development.     

Resection of focal cortical dysplasia located in the upper pre‐central gyrus

The primary motor cortex of the oro‐facial level can be removed without permanent deficits, because of the bilateral representation of the innate functions. In contrast, resective surgery of the hand motor cortex or higher levels presents more challenges. We treated two adult patients with intractable epilepsy caused by small focal cortical dysplasia in the pre‐central gyrus located between the foot and hand primary motor cortices. Focal cortical resection was guided by cortical EEG and intra‐operative motor evoked potential, resulting in seizure freedom without neurological deficits in both cases. These cases illustrate that resective surgery can be safely performed in the primary motor cortex even dorsal to the oro‐facial level, as long as the critical regions of the hand and foot motor cortices remain intact. Accurate delineation of the anatomical lesion and functional areas using intra‐operative neurophysiological monitoring is crucial for successful outcome of the surgery.     

局限性脑皮质发育不良继发顽固性癫痫的手术治疗

目的 探讨局限性脑皮质发育不良（FCD）的诊断、影像学和电生理学特点，以及手术治疗的策略与方法。方法 1996年6月至2003年12月在意大利米兰NiguardaCa’Granda医院手术治疗的442例癫痫患者中，根据该中心提出的FCD病理学分类标准，对81例诊断为FCD的病例进行回顾性研究。其中皮层组织结构发育异常（AD）42例、细胞组织结构发育异常（CD）12例、Taylor脑皮质发育不良（TFCD）27例。患者术前均行MRI、VEEG检查，61％的患者还接受了立体脑电图检查（SEEG）。结果 术前MRI检查阳性率65％。癫痫术后随访1年以上总治愈率为54％（Engle Ia），其中AD组为49％、CD组45％、TFCD组69％。FCD病理分型的不同与癫痫发作频率、致痫灶部位以及手术效果有关。AD组致痫灶常见于颞叶，癫痫发作次数少于CD和TFCD组。而TFCD常发生于颞叶以外的部位，SEEG发作间期显示有典型的放电节律，且手术愈后较好。结论 该分类标准简单且易于操作，对分析临床表现与判定手术效果有指导意义。SEEG技术在研究FCD，特别是TFCD电生理特征有独特的优势，并为术前准确定位致痫灶范围、保证手术效果提供了重要保障。     

磁共振阴性的局灶性脑皮质发育不良的手术治疗

目的探讨磁共振难以确定病灶的致痫性局灶性脑皮质发育不良的诊断和定位方法,提高手术治疗效果。方法回顾性分析联合应用视频脑电图(VEEG)、脑磁图(MEG)及术中皮层电极脑电图监测(ECo G)检查,诊断、定位并经手术后病理证实为局灶性皮质发育不良(FCD)的24例磁共振检查阴性的难治性癫痫患者的临床资料。结果 24例癫痫患者行手术治疗,病理FCDⅠa型5例,FCDⅠb型3例,FCDⅠc型5例,FCDⅡa型6例,FCDⅡb型5例。术后随访1~5年,EngelⅠ级9例,EngelⅡ级5例,EngelⅢ级8例,EngelⅣ级2例。结论联合应用VEEG、MEG和(或)ECo G技术有助于准确诊断和定位磁共振阴性的FCD,提高FCD致难治性癫痫的手术疗效。     

Focal cortical dysplasia of Taylor's balloon cell type: a clinicopathological entity with characteristic neuroimaging and histopathological features, and favorable postsurgical outcome

BACKGROUND AND PURPOSE: Focal cortical dysplasia of Taylor's balloon-cell type (FCD-BC) are a frequent cause of pharmacoresistant epilepsy in young patients. In order to characterize FCD-BC, we coupled MRI and histopathology, and analyzed the clinical outcome following epilepsy surgery. METHODS: From an epilepsy data bank with 547 histological specimens, 17 FCD-BC were re-evaluated of which high resolution MRI was available. Five additional FCD-BC were prospectively identified by MRI. Histopathological and immunohistochemical features were related to MRI. Outcome following lesionectomy was analyzed as determined on routine examinations 3, 6 and 12 months following surgery. RESULTS: All but one lesion were located outside the temporal lobe. A markedly hyperintense funnel-shaped subcortical zone tapering towards the lateral ventricle was the characteristic finding on FLAIR MRI. Histopathologically, the subcortical zone of the FCD-BC displayed hypomyelinated white matter with radially oriented balloon cells and gliosis. Dysplastic neurons were found in the adjacent, disorganized cortex. All patients with complete lesionectomy were seizure free one year following surgery. CONCLUSION: Focal cortical dysplasias of Taylor's balloon-cell type (FCD-BC) have characteristic MRI and histopathological findings. MRI recognition is important, since outcome following resective surgery is favorable.     

Clinical and experimental studies of epilepsy associated with focal cortical dysplasia

The results of clinical and experimental studies on epilepsy associated with focal cortical dysplasia (FCD) are presented. We have been interested in the findings of abnormal increases in the numbers of small vessels in specimens of FCD resected from epilepsy patients. In the clinical study of 13 patients with epilepsy, specimens of FCD or dysembryoplastic neuroepithelial tumor (DNT) were examined using immunohistochemistry. The number of vessels in both lesions were greater than those in cortical specimens of autopsy cases without epilepsy. Because the vessels showed negative staining of VEGF, it was thought that the phenomenon of increase in the number of vessels was simply a hypervascularity, not a neovascularity. The local hypervascularity was expected to show local hyperperfusion in CBF-SPECT study, but interictal SPECT demonstrated local hypoperfusion and ictal SPECT showed hyperperfusion. This may have been caused by a functional change in those vessels. In the experimental study, we tried to make a new animal model of FCD to study epileptogenicity of FCD. When kainic acid had been infused into the neocortex in the neonatal rats, FCD was induced in adult Wistar rats. Histopathological examination revealed cortical dyslamination and abnormal neurons. On EEG, local spike bursts were elicited from the lesions, however, clinical seizures were not detected. Although the data are preliminary and observation over a longer period is required to determine whether spontaneous seizures will occur in this model, it is expected that this new model will be useful for studying epilepsy associated with FCD.     

Ictal SPECT is useful in localizing the epileptogenic zone in infants with cortical dysplasia

Aims. To assess the localizing value of ictal SPECT in very young epilepsy surgery candidates when cerebral haemodynamic responses are known to be immature. Methods. We retrospectively studied 13 infants with intractable focal epilepsy caused by focal cortical dysplasia (FCD). Completeness of resection of the (1) ictal SPECT hyperperfusion zone and (2) cerebral cortex with prominent ictal and interictal abnormalities on intracranial EEG (ECoG or long‐term invasive monitoring) and the MRI lesion, when present, were correlated with postoperative seizure outcome. Results. All five patients with complete resection of the ictal SPECT hyperperfusion zone were seizure‐free compared to only one of eight patients with incomplete or no excision of hyperperfusion zones (p=0.00843). Similar results were noted for the MRI/iEEG‐defined epileptogenic region; five of six patients with complete removal were seizure‐free, whereas only one of seven incompletely resected patients was seizure‐free (p=0.02914). All four patients who underwent complete resection of both regions were seizure‐free compared to none of the six with incomplete resection (p=0.01179). Conclusion. Despite age‐related differences in cerebral perfusion, ictal SPECT provides useful localization data in infants with FCD. Complete resection of the hyperperfused regions is a strong predictor of favourable outcome. The added information may alleviate the need for invasive EEG evaluations in some patients.     

Widespread frontal lobe cortical dysplasia or partial hemimegalencephaly: a continuum of the spectrum

Focal cortical dysplasia (FCD) type II and hemimegalencephaly (HME) are currently considered as a continuum of pathology, the most important distinction being the extent or the size/volume of the lesion. While partial HME involving the posterior cortex has been well described, we present an unusual case with a dysplastic lesion of the whole frontal lobe. A 17‐year‐old boy had focal seizures from the age of nine years. Apart from diminished right‐hand dexterity, his neurological and cognitive status were unremarkable. The course of his epilepsy exhibited a relapsing‐remitting pattern, with prolonged periods of remission. Imaging showed dysplastic left frontal lobe (including paracentral lobule) thickened cortex with an abnormal gyration pattern resembling polymicrogyria, as well as dystrophic calcifications and hypodensity scattered throughout the white matter. This patient represents an intermediate case within the FCD type II/HME spectrum. Localization of the lesion in the frontal lobe as well as clinical characteristics (childhood onset, relapsing‐remitting epilepsy, without hemiparesis and overt cognitive impairment) are more consistent with FCD type II, while a range of MRI features is shared between HME and FCD type II.     

Three-dimensional brain surface visualization for epilepsy surgery of focal cortical dysplasia

Focal cortical dysplasia (FCD) causes medically intractable seizures in 5–10% of adult epilepsy patients, but patients can become seizure free through surgical resection. The authors present the utility of three-dimensional surface visualization (3DSV) that expands on existing imaging datasets to highlight surface vasculature as a tool for achieving more successful resections in patients with FCD. In this prospective series of six patients, preoperative 3DSV was performed for planning the surgical approach to the lesion and for intraoperative guidance. Reconstructions involved volume rendering of a contrast-enhanced dataset to visualize surface venous vasculature. Postoperatively, five of the six patients had complete resections, with one patient having a subtotal resection due to proximity to crucial vasculature. We report that 3DSV is a useful tool for surgical planning, since topographical relationships between lesion location and surface vasculature landmarks are less likely to change with surgical progress.     

脑皮质发育不良继发顽固性癫痫的病理分型及手术治疗

目的 探讨局灶性脑发育不良(FCD)的临床特征、病理学、影像学的特点及手术疗效.方法 42例外科手术切除致痫灶并经病理证实为FCD的患者中,根据Palmini病理学分型进行分类,并对其临床特征、影像学特点及手术疗效进行回顾性分析.结果 42例患者中,按致痫灶部位分类颢叶24例、额叶14例、顶叶6例及枕叶3例,其中多脑叶5例.术前影像学检查阳性率62%.组织学分型FCDⅠA型9例,FCDⅠB型21例,FCDⅡA型5例,FCDⅡB型7例,其中以FCD Ⅰ B型最为常见,多位于颞叶且常伴有海马硬化.所有患者术后至少随访1年以上,癫痫术后治愈率FCD位于颞叶67%,颞叶以外43%(EngleⅠa).结论 FCD是难治性癫痫常见的病理学改变,其病理分型与临床特征和致痫灶部位存在相关性,为制定手术方案和判定手术效果提供了依据.     

Abnormal local-circuit neurons in epilepsia partialis continua associated with focal cortical dysplasia

Summary A limited cortical resection including the rolandic fissure and the pre-and postcentral cortical regions was carried out in a patient suffering from epilepsia partialis continua resistant to antiepileptic drugs. The histological examination revealed several foci of very large neurons distributed with no laminar organization in the depth of the rolandic fissure and in the crown of the primary motor and primary somatosensory areas; these lesions were consistent with focal cortical dysplasia. In addition, decreased numbers of neurons, astrocytosis and proliferation of capillaries, compatible with chronic tissue necrosis, were found in the inferior regions of the banks of the rolandic fissure. Subpopulations of local-circuit neurons were examined with parvalbumin, calbindin D-28k and somatostatin immunocytochemistry. Focal areas of cortical dysplasia contained abnormal immunoreactive neurons. Huge parvalbumin-immunoreactive cells were distributed at random and resembled axo-axonic (chandelier) and basket neurons. Abnormal calbindin D-28k-immunoreactive cells were reminiscent of double-bouquet neurons and multipolar cells. Very large somatostatin-immunoreactive cells were seldom observed in the dysplastic foci. On the other hand, areas of tissue necrosis displayed massive reduction of immunoreactive cells and fibers. Abnormalities in the morphology and distribution of local-circuit (inhibitory) neurons observed here for the first time in focal cortical dysplasia may have a pivotal role in the appearance and prolongation of electrical discharges and continuous motor signs in human focal epilepsy.Supported in part by a grant FIS 90E1263